T cells may be triggered to undergo apoptosis by several stimuli. For example, antigen binding to the T cell receptor (TCR) induces apoptosis. Glucocorticoids and exposure to either ionizing or UV radiation also results in cell death. The ultimate death of the cell may be prevented, in all of these cases, by treatment with actinomycin D, indicating new gene synthesis is required- Through the use of subtractive screening strategies and, more recently, by constructing subtracted libraries, my lab has cloned several genes that are either induced or repressed during cell death. One gene we identified as induced during T cell death through the TCR pathway is nur77, a member of the steroid-thyroid hormone receptor superfamily. This gene is required for TCR-mediated cell death since antisense inhibition of the gene prevents cell death. Members of the steroid-thyroid hormone family are known to act as transcription factors. These genes are characterized by a well-conserved zinc finger domain that regulates DNA binding. There are relatively few DNA elements recognized by the numerous members of this family suggesting that their many regulatory effects are not mediated exclusively through DNA binding. Rather, it is thought that specific effects may be the result of protein/protein interactions. This proposal will use the yeast two-hybrid system to identify potential protein partners of Nur77.